Methods and apparatus for enhanced fiducial point determination and non-invasive hemodynamic parameter determination

ABSTRACT

Methods and apparatus for utilizing multiple sources of physiologic data to enhance measurement robustness and accuracy. In one embodiment, phonocardiography or “heart sounds” data is used in combination with one or more other techniques (for example, impedance cardiography or ICG waveforms, and/or electrocardiography or ECG waveforms) to provide more accurate and robust physiological and/or hemodynamic assessment of living subjects. In one variant, the aforementioned methods and apparatus are used to improve ICG fiducial point (e.g., B, C and X point) detection and identification accuracy. Moreover, the new ICG fiducial points that may be clinically important may be identified using the disclosed methods and apparatus. In a further aspect, the invention discloses methods and apparatus for utilization of ICG and/or ECG waveform information to improve the identification and characterization of heart sounds (such as e.g., S1, S2, S3, or S4 heart 20 sounds), murmurs, and other such artifacts or phenomena.

PRIORITY

The present application claims priority benefit of U.S. provisionalpatent application Ser. No. 60/919,725 filed Mar. 23, 2007 of the sametitle, which is incorporated herein by reference in its entirety.

COPYRIGHT

A portion of the disclosure of this patent document contains materialthat is subject to copyright protection. The copyright owner has noobjection to the facsimile reproduction by anyone of the patent documentor the patent disclosure, as it appears in the Patent and TrademarkOffice patent files or records, but otherwise reserves all copyrightrights whatsoever.

1. FIELD OF THE INVENTION

This invention relates generally to the field of physiologic analysis ofliving subjects, and particularly in one exemplary aspect to anapparatus and methods for non-invasively detecting and evaluating thecardiac or hemodynamic function of a subject using, inter alia, heartsounds.

2. DESCRIPTION OF RELATED TECHNOLOGY

In the field of assessing cardiac or hemodynamic function in a livingsubject, a multitude of techniques currently exist. One such technologyfor assessing cardiac function is the well known electrocardiogram orECG. An ECG is an output produced by an electrocardiograph whichillustrates (e.g., graphically) the electrical activity of the subject'sheart over time. By utilizing ECG techniques, diagnostic informationabout the cardiac function of a living subject can be obtained. Amongother applications, ECG has become particularly well known for its usein detecting cardiac arrhythmias.

On such example of the use of ECG technology is disclosed in U.S. Pat.No. 6,947,789 to Selvester, et al. issued Sep. 20, 2005 and entitled“Method for detecting, sizing and locating old myocardial infarct” whichdiscloses algorithms for detecting, sizing and locating old myocardialinfarcts by evaluating ECG lead data derived from selected ECG leads.For a given human subject, the specific hierarchical pattern of leaddata to be examined is selected on the basis of predetermined personaland demographic data.

So called impedance cardiography (ICG), also referred to as thoracicelectrical bio-impedance (TEB) and electrical impedance plethysmography(EIP) is another common prior art method for assessing cardiac orhemodynamic function in a living subject. ICG utilizes the placement ofsensors (typically on the neck and chest or thorax of the subject) whichare then used to transmit and detect electrical and impedance changes inthe thorax of a living subject. These electrical and impedance changesare then used to measure and calculate various hemodynamic parameters ofthe living subject. Exemplary ICG devices and techniques are describedin, inter alia, U.S. Pat. No. 6,561,986 to Baura, et al. issued May 13,2003 entitled “Method and apparatus for hemodynamic assessment includingfiducial point detection” U.S. Pat. No. 6,602,201 to Hepp, et al. issuedAug. 5, 2003 and entitled “Apparatus and method for determining cardiacoutput in a living subject”, U.S. Pat. No. 7,043,293 to Baura issued May9, 2006 entitled “Method and apparatus for waveform assessment”, andU.S. Pat. No. 7,149,576 to Baura, et al. issued Dec. 12, 2006 entitled“Apparatus and method for defibrillation of a living subject”, each ofthe foregoing being incorporated herein by reference in its entirety.

The recording of heart sounds (i.e. the sounds generated by the beatingheart and/or the resultant flow of blood) is another technique utilizedto ascertain cardiac and/or hemodynamic function of a living subject. Inthe well known technique of cardiac auscultation, a caregiver uses astethoscope to listen for these sounds, which can also provide importantclues into the condition of the heart. There are four major functionalareas of auscultation of the heart (i.e., aortic, pulmonic, tricuspid,and mitral. They are named for the valve that they best assess.

Normal human heart sounds are produced by, inter alia, closure of thevalves of the heart muscle. Flow through these valves will affect thesound made. Thus, in situations of increased blood flow (e.g., strenuousexercise), the intensity of the heart sounds may be increased. Insituations of lower blood flow (e.g., shock), the intensity of the heartsounds may be decreased.

Normal heart sounds include so-called S1 and S2 sounds. The S1 sound isnormally the first heart sound heard (best heard in the mitral area),and corresponds to closure of the mitral and tricuspid (AV) valves, aswell as the opening of the aortic valve. A normal S1 sound is typicallylower-pitched, and of longer duration than, S2.

The S2 sound is normally the second sound heard (best heard over theaortic area), and corresponds to closure of the pulmonic and aorticvalves. A normal S2 is higher-pitched and of shorter duration than S1.S2 is also normally louder (greater amplitude) than S1.

Abnormal human heart sounds comprise the S3 and S4 sounds. The S3 soundis heard immediately following S2, and may be considered normal inchildren and adolescents, but usually disappears in adults. When heardin adults, an S3 may indicate left ventricular failure.

The S4 sound is heard immediately before the S1. It may be present ininfants and children. The S4 is produced by a decreased compliance ofthe ventricle, and may indicate myocardial infarction (i.e., heartattack) or shock.

Many factors can affect heart sounds in a human, and may producealterations in both the normal and abnormal sounds. These include forexample congenital defects, previous cardiac disease, and patient age.

Moreover, heart murmurs may be generated by a turbulent flow of blood,and may occur inside or outside the heart. Abnormal murmurs can becaused by, inter alia, stenosis or a restriction of the opening of aheart valve, causing turbulence as blood flows through it. Valveinsufficiency (or regurgitation) allows backflow of blood when theincompetent valve is supposed to be closed. Different murmurs areaudible in different parts of the cardiac cycle, depending on the causeof the murmur.

More recently, techniques have been proposed which combine differingcardiac assessment techniques (such as ECG and heart sounds) in order toimprove the assessment of cardiac function in a living subject. Forexample, U.S. Pat. No. 4,548,204 to Groch, et al. issued Oct. 22, 1985and entitled “Apparatus for monitoring cardiac activity via ECG andheart sound signals” discloses a technique where from a heart soundsignal input the occurrence of a first occurring heart sound isdetected. Thereupon a predetermined heart sound enable window time isestablished, which for a first detection cycle is set to approximatelythe diastolic interval for the maximum heart rate to be detected. If asecond heart sound occurs within this heart sound enable window time,this second heart sound is detected as a systole heart sound. The firstheart sound may be detected as a diastole heart sound. If a second heartsound does not occur within the heart sound enable window time theprocedure is repeated with increasing heart sound enable time as long asa second heart sound occurs within an increased heart sound enablewindow time. For monitoring remotely or by a using recording, an ECGsignal is modulated and combined with the associated heart sound signalfor use as a single combined signal.

U.S. Pat. No. 7,096,060 to Arand, et al. issued Aug. 22, 2006 andentitled “Method and system for detection of heart sounds” discloses amethod and system for automatically detecting heart sounds. The soundsystem receives sound data corresponding to beats of the heart. Thesound system analyzes the sound data to detect the presence of a heartsound within the beats. The sound system then outputs an indication ofthe heart sounds that were detected. The sound system may use ECG datato identify various locations (e.g., R peak) within a beat and use thoselocations to assist in the detection of heart sounds.

U.S. Pat. No. 7,139,609 to Min, et al. issued Nov. 21, 2006 and entitled“System and method for monitoring cardiac function via cardiac soundsusing an implantable cardiac stimulation device” discloses techniquesfor performing internal measurement of heart sounds to estimate patientcardiac function in terms of stroke volume, cardiac output, or a maximumrate of change of aortic pressure with time (max dP/dt). Controlparameters of the medical device are then automatically adjusted so asto optimize overall cardiac function or to provide for ventricularresynchronization therapy. In one example, heart sound signals arederived from acceleration signals received from an accelerometer. Theheart sound signals are analyzed to identify S and S2 heart sounds aswell as ejection period and isovolumic interval (ISOV). Proxies for maxdP/dt, stroke volume and cardiac output are then derived from the S1 andS2 heart sounds, the ejection period and the ISOV. Alternativetechniques, not requiring detection of ISOV, are also disclosed andemployed for use if the patient has heart value regurgitation.

United States Patent Publication No. 20020151938 to Corbucci, publishedon Oct. 17, 2002 and entitled “Myocardial performance assessment”discloses a technique whereby myocardial performance is assessed using acombination of electrical and mechanical criteria. More specifically,this assessment may be based on a QT interval based on electrogram (EGM)readings and on first and second heart sounds. The timing relationshipsbetween the QT interval and the first and second heart sounds can beused to evaluate certain systolic, diastolic, and systolic/diastolicparameters relating to myocardial performance. In addition, theseparameters may be used to drive therapies. For example, myocardialperformance parameters obtained from the QT interval and from the timingof the first and second heart sounds may be used to optimize the AVdelay and to optimize multi-site pacing.

United States Patent Publication No. 20040167417 to Schulhauser, et al.published Aug. 26, 2004 and entitled “Apparatus and method forchronically monitoring heart sounds for deriving estimated bloodpressure” discloses a minimally invasive, implantable heart sound andECG monitor and associated methods for deriving blood pressure fromheart sound data. The device is equipped with an acoustical sensor fordetecting first and second heart sounds which are sampled and storedduring sensing windows following R-wave and T-wave detections,respectively. ECG and heart sound data are stored in a continuous,looping memory, and segments of data are stored in long-term memory uponan automatic or manual data storage triggering event. Estimated bloodpressure is calculated based on custom spectral analysis and processingof the first and second heart sounds. A calibration method includesmeasuring a patient's blood pressure using a standard clinical methodand performing regression analysis on multiple spectral variables toidentify a set of best fit weighted equations for predicting bloodpressure. Concurrent ECG and estimated blood pressure may be displayedfor review by a physician.

United States Patent Publication No. 20040254481 to Brodnick, publishedDec. 16, 2004 and entitled “Methods and systems for monitoringrespiration” discloses a method for determining respiration rate in apatient that can include various parts. The respiration rate can bedetermined by measuring the heart's S2 split. The S2 split can beidentified by observing the timing of the heart sounds. Otherrespiration related information, such as respiration phase and theoccurrence of apnea, can be identified as well. A respiration monitor ofthis type may be useful for monitoring sub-acute patients, andoutpatients. A sensor for the respiration monitor and an electrode foran ECG monitor may be combined into a single probe.

United States Patent Publication No. 20060100535 to Bauer published May11, 2006 and entitled “Integrated, plural-signal, heart-signal sensorsystem and related data-presentation methodology” discloses a system anda related methodology for gathering, during a selected time span, andfrom a common anatomical site, time-contemporaneous ECG-electrical andheart-sound signals including (1) processing such signals to effect (a)time-based, related ECG fiducials, and (b) systolic and diastolicheart-sound indicators, and (2) creating a reportable data stream whichcommunicates such effected fiducials and indicators in a manner wherebytime-based relationships between them, and non-time-baseddifferentiation between systolic and diastolic heart-sound indicators,are made visually discernible. The methodology of the invention may alsobe implemented strictly for the gathering and processing of heartsounds.

Despite the foregoing variety of techniques, there remains a salientneed for improved apparatus and methods for the assessment of cardiacand/or hemodynamic function in a living subject, including especiallythe diagnosis of particular cardiac and hemodynamic conditions andphenomena within the subject being evaluated. Ideally, such improvedapparatus and methods would make use of technologies generally familiarto practitioners while offering additional tools and techniques whichprovide, for example, confirmatory analysis of observedcardiac/hemodynamic function. Such improved apparatus and methods wouldalso add to and utilize the strengths of existing techniques, whilesimultaneously minimizing the drawbacks of those same techniques throughthe combination of differing but complementary analyses.

SUMMARY OF THE INVENTION

The present invention satisfies the foregoing needs by providing, interalia, improved apparatus and methods for cardiac function assessment.

In a first aspect of the invention, a method of assessing cardiacfunction within a living subject is disclosed. In one embodiment, themethod comprises: obtaining: (i) acoustic information relating to thecardiac system of said subject; (ii) electrocardiographic informationrelating to said subject; and (iii) impedance cardiographic informationrelating to said subject; and utilizing said acoustic,electrocardiographic and impedance information substantially in concertto assess cardiac function.

In a second aspect of the invention, a method of evaluating or detectingone or more acoustic artifacts or features within a waveform isdisclosed. In one embodiment, the method comprises using a knownfiducial point in a first waveform (e.g., R point within ECG) toidentify or validate one or more heart sounds (e.g., S1 or S2).

In a third aspect of the invention, an improved method of determining atleast one hemodynamic parameter or function associated with a livingsubject is disclosed. In one exemplary embodiment, the hemodynamicparameter comprises cardiac output, and the method comprises utilizingheart sounds in conjunction with ICG and ECG signals to provide acardiac output measurement of improved accuracy and robustness.

In a fourth aspect of the invention, a method of detecting specificevents or artifacts within a hemodynamic parametric waveform isdisclosed. In one exemplary embodiment, the waveform comprises a heartsounds acoustic waveform, and the method comprises using an R point ofan ECG to more accurately detect the S1 and S2 events (as well asdetection of specific areas or features of the S and S2 sounds). Inanother embodiment, the waveform comprises an ICG waveform, and themethod comprises using the S1 and S2 events to more accurately detectartifacts of interest (e.g., aortic valve operation). By more accuratelydetecting these hemodynamic parameters and events, results of therapycan be monitored, trends can be better tracked, and other suchevaluations conducted that would not be feasible with less accuratemeasurements.

In a fifth aspect of the invention, an improved computer program forimplementing the aforementioned methods is disclosed. In a firstexemplary embodiment, the computer program comprises an object coderepresentation of an assembly language source code listing, the objectcode representation being disposed on a transportable storage medium(e.g., floppy disk). In a second embodiment, the computer program isdisposed on the discrete storage device of a signal processing apparatusand adapted to run on the digital processor thereof. The computerprogram further comprises a graphical user interface (GUI) operativelycoupled to the display and input device of the signal processingapparatus. One or more subroutines or algorithms for implementing themethodologies above are included within the program. In a thirdexemplary embodiment, the computer program comprises an instruction setdisposed within the storage device (such as the embedded program memory)of the digital signal processor (DSP) of the signal processingapparatus.

In a sixth aspect of the invention, an improved apparatus for assessingone or more hemodynamic parameters associated with a living subject isdisclosed. In one exemplary embodiment, the hemodynamic parameter underevaluation comprises the cardiac output of the subject, and theapparatus generally comprises a plurality of electrodes disposed inproximity to the thoracic cavity of the subject; a current sourceadapted to provide a predetermined current through the thoracic cavityof the subject via at least one of the plurality of electrodes; and asignal processing apparatus adapted to analyze the signals obtained fromthe electrodes and determine stroke volume (and accordingly cardiacoutput) therefrom. The signal processing apparatus comprises a signalconditioning apparatus adapted to process signals (including theimpedance signal(s), heart sounds and ECG derived from one or more ofthe electrodes) and produce conditioned signals relating thereto; and aprocessor adapted to detect the fiducial points within the impedancesignal(s) or conditioned signals, from which cardiac output isultimately determined.

In a seventh aspect of the invention, an improved method of providingtreatment to a subject using the aforementioned methodology isdisclosed.

In an eighth aspect, an improved physiologic sensor is disclosed. In oneembodiment, the sensor comprises a disposable sensor that integratesheart sounds, ICG and ECG signal capability into one apparatus.

In a ninth aspect of the invention, methods and apparatus for increasingthe clinical robustness of a physiologic determination system aredisclosed. In one embodiment, the system comprises an ICG system, andthe methods/apparatus utilize one or more heart sounds to aid invalidation and/or detection of artifacts or features in the ICGwaveform.

In a tenth aspect of the invention, improved defibrillation apparatusand methods using heart sound, ICG and ECG data are disclosed.

In an eleventh aspect of the invention, methods and apparatus for theidentification of one or more physiologic conditions using heart soundsinformation coupled with ICG and/or ECG data is disclosed.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a logical flow diagram illustrating one embodiment of thegeneralized method of using multiple sources of physiologic informationto increase the robustness of a physiologic measurement ordetermination.

FIG. 1a is a logical flow chart illustrating one specific implementationof the generalized method of FIG. 1 in the context of heartsounds/CG/ECG data.

FIG. 1b is a logical flow diagram illustrating one embodiment of themethod of identifying a particular condition (e.g., impending or actualheart failure) using the multi-source approach of the invention.

FIG. 2a is a top elevational view of one embodiment of a disposablesensor apparatus with unified detection capability according to thepresent invention.

FIG. 2b is a cross-sectional view of the sensor of FIG. 2a , taken alongline 2 b-2 b, showing the details thereof.

FIG. 2c is a cross-sectional view of another embodiment of the sensor ofthe invention, wherein a piezoelectric or piezoresistive film or layeris used.

FIG. 3 is a block diagram of one exemplary embodiment of the apparatusfor hemodynamic assessment according to the invention.

FIG. 4 is a logical flow diagram illustrating one exemplary embodimentof the method of providing treatment to a subject using theaforementioned methods and apparatus.

DETAILED DESCRIPTION OF THE INVENTION

Reference is now made to the drawings wherein like numerals refer tolike parts throughout.

As used herein, the term “software application” refers generally to aunit of executable software that implements a certain functionality ortheme. The themes of applications vary broadly across any number ofdisciplines and functions (such as on-demand content management,e-commerce transactions, brokerage transactions, home entertainment,calculator etc.), and one application may have more than one theme. Theunit of executable software generally runs in a predeterminedenvironment; for example, the unit could comprise a downloadable JavaXlet™ that runs within the JavaTV™ environment.

As used herein, the term “computer program” or “software” is meant toinclude any sequence or human or machine cognizable steps which performa function. Such program may be rendered in virtually any programminglanguage or environment including, for example, C/C++, Fortran, COBOL,PASCAL, assembly language, markup languages (e.g., HTML, SGML, XML,VoXML), and the like, as well as object-oriented environments such asthe Common Object Request Broker Architecture (CORBA), Java™ (includingJ2ME, Java Beans, etc.), Binary Runtime Environment (e.g., BREW), andthe like.

As used herein, the term “display” means any type of device adapted todisplay information, including without limitation CRTs, LCDs, TFTs,plasma displays, LEDs, incandescent and fluorescent devices. Displaydevices may also include less dynamic devices such as, for example,printers, e-ink devices, and the like.

As used herein, the term “integrated circuit (IC)” refers to any type ofdevice having any level of integration (including without limitationULSI, VLSI, and LSI) and irrespective of process or base materials(including, without limitation Si, SiGe, CMOS and GaAs). ICs mayinclude, for example, memory devices (e.g., DRAM, SRAM, DDRAM,EEPROM/Flash, ROM), digital processors, SoC devices, FPGAs, ASICs, ADCs,DACs, transceivers, memory controllers, and other devices, as well asany combinations thereof.

As used herein, the terms “Internet” and “internet” are usedinterchangeably to refer to inter-networks including, withoutlimitation, the Internet.

As used herein, the term “memory” includes any type of integratedcircuit or other storage device adapted for storing digital dataincluding, without limitation, ROM. PROM, EEPROM, DRAM, SDRAM, DDR/2SDRAM, EDO/FPMS, RLDRAM, SRAM, “flash” memory (e.g., NAND/NOR), andPSRAM.

As used herein, the terms “microprocessor” and “digital processor” aremeant generally to include all types of digital processing devicesincluding, without limitation, digital signal processors (DSPs), reducedinstruction set computers (RISC), general-purpose (CISC) processors,microprocessors, gate arrays (e.g., FPGAs), PLDs, reconfigurable computefabrics (RCFs), array processors, secure microprocessors, andapplication-specific integrated circuits (ASICs). Such digitalprocessors may be contained on a single unitary IC die, or distributedacross multiple components.

As used herein, the terms “network” refers generally to any type oftelecommunications or data network including, without limitation, hybridfiber coax (HFC) networks, satellite networks, telco networks, and datanetworks (including PANs, MANs, WANs, LANs, WLANs, piconets, micronets,internets, and intranets). Such networks or portions thereof may utilizeany one or more different topologies (e.g., ring, bus, star, loop,etc.), transmission media (e.g., wired/RF cable, RF wireless, millimeterwave, optical, etc.) and/or communications or networking protocols(e.g., SONET, DOCSIS, IEEE Std. 802.3, ATM, X.25, Frame Relay, 3GPP,3GPP2, WAP, SIP, UDP, FTP, RTP/RTCP, H.323, etc.).

As used herein, the term “network interface” refers to any signal, data,or software interface with a component, network or process including,without limitation, those of the Firewire (e.g., FW400, FW800, etc.),USB (e.g., USB2), Ethernet (e.g., 10/100, 10/100/1000 (GigabitEthernet), 10-Gig-E, etc.), MoCA, Serial ATA (e.g., SATA, e-SATA,SATAII), Ultra-ATA/DMA, Coaxsys (e.g., TVnet™), radio frequency tuner(e.g., in-band or OOB, cable modem, etc.), WiFi (802.11a,b,g,n), WiMAX(802.16), PAN (802.15), or IrDA families.

As used herein, the term “signal” refers to any electrical, optical,electromagnetic, subatomic, thermal, chemical/electro-chemical, or othertransferal of information. Such signal may be, without limitation, inthe analog or digital domain, or otherwise. Specific examples of signalsinclude waveforms, pulses, binary digital data, analog voltage levels,modulated radio or infrared waves, including temporal and/or spatialvariations of any of the foregoing.

As used herein, the term “storage device” refers to without limitationcomputer hard drives, DVR device, memory, RAID devices or arrays,optical media (e.g., CD-ROMs, Laserdiscs, Blu-Ray, etc.), or any otherdevices or media capable of storing content or other information.

As used herein, the term “user interface” refers to, without limitation,any visual, graphical, tactile, audible, sensory, or other means ofproviding information to and/or receiving information from a user orother entity.

As used herein, the term “wireless” means any wireless signal, data,communication, or other interface including without limitation WiFi,Bluetooth, 3G, HSDPA/HSUPA, TDMA, CDMA (e.g., IS-95A, WCDMA, etc.),FHSS, DSSS, GSM, PAN/802.15, WiMAX (802.16), 802.20, narrowband/FDMA,OFDM, PCS/DCS, analog cellular, CDPD, satellite systems, millimeter waveor microwave systems, acoustic, and infrared (i.e., IrDA).

Overview

In one fundamental aspect, the present invention comprises methods andapparatus for utilizing phonocardiography or “heart sounds” incombination with one or more other techniques (for example, impedancecardiography or ICG waveforms, and/or electrocardiography or ECGwaveforms) to provide more accurate and robust physiological and/orhemodynamic assessment of living subjects. In effect, one exemplaryimplementation of the invention utilizes an ensemble of hemodynamicallysignificant (or potentially significant) events to better, inter alia,identify fiducial points and assess cardiac and hemodynamic systemfunction.

In one variant, the aforementioned methods and apparatus are used toimprove ICG fiducial point (e.g., so-called B, C and X point) detectionand identification accuracy. Moreover, the new ICG fiducial points thatmay be clinically important may be identified using the disclosedmethods and apparatus.

In another aspect, the combination of heart sounds with ICG and/or ECGsignals is used to better identify and assess hemodynamic information(such as PEP (pre-ejection period), LVET (left ventricular ejectiontime), Ejection Fraction, Regurgitation, conduction problems, valvulardefects, stenosis, or reduced ejection fraction, etc.) through e.g., theuse of the aforementioned improvements in fiducial point determination,and/or in the presentation of additional information that permits betterclassification of ICG waveforms obtained from the subject.

In a further aspect, the invention discloses methods and apparatus forutilization of ICG and/or ECG waveform information to improve theidentification and characterization of heart sounds (such as e.g., S1,S2, S3, or S4 heart sounds), murmurs, and other such artifacts orphenomena.

In another aspect of the invention, the physiological process ofregurgitation can be identified and/or assessed using the presentinvention. This provides a more accurate confirmation of the presence ofregurgitation, or alternatively localizes where to look for the event.

In another aspect of the invention, the length (duration) of one or moreheart sounds is determined and used for inter alia fiducial point orartifact/event identification or location.

In yet another variant, the duration of the heart sound(s) relative toQRS complex duration or length is evaluated. This approach givesinformation regarding the electrical activity of the heart relative toits aural activity. Moreover, the position of one or more ICG fiducialpoints within the heart sound(s) itself may be determined and evaluated.

While broadly applicable to many different types, species, conditionsand dispositions of living subjects, the present invention findsparticular utility with respect to monitoring more degraded heartfailure patients where the blood flow hemodynamic properties may be verydifferent (and often more challenging to detect and interpret) thanthose of normal, healthy patients.

DESCRIPTION OF EXEMPLARY EMBODIMENTS

Exemplary embodiments of the present invention are now described indetail. It is noted that while the exemplary embodiments of theinvention is described herein in terms of an apparatus and methods fordetermining, inter alia, fiducial points and non-invasive hemodynamicmeasurements (e.g., cardiac output) suitable for use on the thorax of ahuman subject, the invention may also be embodied or adapted to use atother locations on the human body, as well as on other warm-bloodedspecies such as, for example, primates, canines, or porcines. All suchadaptations and alternate embodiments are considered to fall within thescope of the claims appended hereto.

Methods—

The methodology of the present invention generally involves using onesource of physiological data (and features or events associatedtherewith) to corroborate or detect other features or events in othersources of data, thereby enhancing the robustness and accuracy of theoverall measurement(s).

FIG. 1 illustrates this generalized methodology graphically. In onespecific embodiment of the method 100 (see FIG. 1a ), the ECG “R” markeris used as a reference for confirming the timing of S1 and S2 heartsounds. As is well known to those of ordinary skill in the art, the S1and S2 heart sounds correspond to aortic valve opening and closing,which are also associated with the “B” point and the “X” point in theICG waveform. Since the B and X points are used in ICG techniques todetermine hemodynamic parameters, by using the very reliable ECG “R”point to more reliably detect and/or validate S1 and S2 heart sounds,and then by using these sounds to more accurately detect X and B pointsin the ICG waveform, then the hemodynamic parameters can be determinedmore accurately.

As shown in FIG. 1, the generalized method 100 comprises first obtaininga waveform from the subject (step 102). In the present embodiment, thiscomprises an ECG waveform, although it will be appreciated that otherwaveforms may be used depending on context.

Next, one or more markers or features (e.g., R point) is identifiedwithin the obtained waveform per step 104.

Per step 106, the identified marker(s) is used to evaluate, confirm, orvalidate the timing of other data. In the present embodiment, the otherdata comprises phonocardiographic data (e.g., heart sounds) having S1and S2 events (or sub-portions or features thereof), and the R point isused to validate the timing of these S1 and/or S2 events. S1 and S2detection algorithms are known in the art; see, e.g., the technology setforth in U.S. Pat. No. 7,096,060 to Arand, et al. issued Aug. 22, 2006and entitled “Method and system for detection of heart sounds”,incorporated herein by reference in its entirety. Accordingly, suchalgorithms are not described further herein.

In one embodiment, the S1 sound is of particular interest (due in largepart to its coupling to the opening of the aortic valve).

Once the timing of the events has been validated, the validated sound(s)is/are used to detect or evaluate one or more features or artifacts inanother waveform (e.g., the B and X fiducial points within the ICGwaveform) per step 108. Any number of different mechanisms for fiducialpoint detection may advantageously be used consistent with the presentinvention; see e.g., U.S. Pat. No. 6,561,986 issued May 13, 2003entitled “Method and Apparatus for Hemodynamic Assessment includingFiducial Point Detection”, incorporated herein by reference in itsentirety, for one such exemplary technique.

In another variant of the method, the first waveform of step 102 above(e.g., the ECG signal) is used to first locate the “R” point reference;this information is then used to identify S1 and/or S2 heart sounds fromthe phonocardiographic data. These S1 and S2 heart sounds may not beable to be otherwise reliably identified due to, e.g., ambient noise orwaveform corruption. However, by using the R point or other fiducialreference having a known correlation with the sounds, the identificationof the S1 and S2 sounds achieves a much higher level of confidence. Thiscan also lead to higher confidence in other heart sounds such as e.g.,murmurs, or S3 and S4 heart sounds.

Accordingly, one embodiment of the invention comprises generating aconfidence measure or parameter using the R point technique describedabove to indicate to a clinician or caregiver (or even an algorithm orautomated system) when the sounds are reliably detected. It will beappreciated that this confidence measure may comprise any number offorms, such as for example and without limitation: (i) a “go/no-go”parameter or gating criterion; (ii) a metric (e.g., “percentconfidence”) which merely advises the clinician or caregiver as to therelative confidence level of the measurement; (iii) an input to ananalysis or evaluation algorithm which uses this information along withother data to arrive at a derivate quantity or recommendation; and/or(iv) an input to a historical, anecdotal or other database such as for“matching” of the detected data to one or more patterns or templates asan aid to classification or recognition. The confidence measure (or anyderivative parameters) may be a linear or non-linear quantity, or mayutilize a fuzzy logic or other such approach (e.g., “low confidence”,“moderate confidence”, “high confidence”) of the type well known in thesignal processing arts. In another embodiment, the relative or absolute“quality” of data (e.g., a beat) can be assessed, and this informationcan be used for any number of purposes such as e.g. (i) selection orreplacement of a reference beat (i.e., one that is used as a standard orreference for other measurements or comparisons); and (ii) determiningwhether a given data (e.g., beat) is suitable to be included within anensemble average or other such technique which uses two or more beats.

In one embodiment of the invention, cardiac waveforms obtained from asubject may be processed using techniques generally associated withbigeminy and trigeminy processing and evaluation. As is well known,bigeminy is a condition wherein premature beats of the heart alternate(typically regularly) with normal beats. Generally harmless, bigeminy isgenerally either atrial or ventricular in nature, depending upon whetherthe alternating premature beats are atrial or ventricular. In caseswhere the premature beats alternate regularly, bigeminy sounds in effectlike a “regularly irregular” heart rhythm.

Similarly, so-called “trigeminy” comprises another abnormal but usuallyharmless rhythm. In trigeminy, one ventricular premature complex (VPC)occurs after every two normal QRS complexes (hence the term “tri”). Notethat in this trigeminic rhythm, two VPCs never occur sequentially (i.e.,one after the other). See, e.g., U.S. Pat. No. 7,146,206 to Glass, etal. issued Dec. 5, 2006 entitled “Detection of cardiac arrhythmia usingmathematical representation of standard ARR probability densityhistograms”, incorporated herein by reference in its entirety, for oneexample of bigeminy/trigeminy processing techniques useful with thepresent invention.

Hence, in the current embodiment of the invention, waveforms obtainedfrom the subject can be electronically parsed into two or more “bins” sothat they may be evaluated, and classified/treated differently ifdesired. This “binning” could be accomplished for example by identifyinguniquely repetitive classes of heartbeats. For instance, heartbeats mayhave different, unique repetitive relationships between the electricalconduction characteristics (as modeled by ECG) and the mechanicalbeat/flow characteristics as modeled by impedance (e.g., ICG). This typeof processing by separation could improve accuracy, and alsoadvantageously avoids possible errors or misdiagnoses. Thisfunctionality may be user-configurable or selectable as well. Forexample in one variant of the invention, a waveform processing algorithmis adapted to evaluate the shape of successive beats or artifacts in thewaveform(s) being processed, and segregate them into separate processingbins. Alternatively, the user (e.g., physician, etc.) may view thewaveform and utilize their intrinsic knowledge and skill to recognizethe various different types of shapes or artifacts, and segregate themaccordingly (such as via a PC or touch-screen user interface, such as aGUI) that allows the user to readily select or classify different typesof artifacts they see). In many cases, the human eye/mind is much moreefficient at recognizing patterns (especially some that may be somewhatsubtle), and can also advantageously make “judgment calls” on beats orartifacts which are not clear cut.

It will also be appreciated that the foregoing approach affords theclinician, in certain circumstances, the ability to look at cardiacoutputs for two or more different conduction paths/modes. Many prior artsystems effectively presume the existence of one conduction path throughthe thorax/cardiac muscle, or at least aggregate the data (which mayhave components of multiple conduction paths inherent therein). Incontrast, the aforementioned embodiment of the present invention allowsfor intelligent parsing or separation of data from different conductionpaths, and evaluation thereof. More specifically, different electricalconduction paths for the heart muscle may be identified by the fact thatthey produce very different impedance waveforms, and valve timing ascharacterized and confirmed by ICG and by heart sounds relative to theECG waveform characteristics. In one exemplary embodiment of theinvention, an ECG waveform (indicative of inter alia the electricalactivity of the heart) is obtained. The mechanical aspects of theheart's operation are then evaluated (e.g., via impedance or ICG),including for example evaluating changes in the ICG. Additionally, thetiming of the heart valves can also be determined via heart soundsmonitoring. By evaluating all of this data (ECG, ICG and heart sounds)in concert, valuable insight into different electrical conduction pathsthrough the heart muscle are obtained. For example, one conduction pathmight yield a very different ECG/ICG/heart sounds composite “profile”than another conduction path, and/or the relationship of the variousdata to each other (e.g., relative timing, amplitude, etc.) may varyacross different conduction paths. Hence, in one respect, the presentinvention allows for a more detailed profile of the heart in terms ofelectrical, mechanical and auditory activity, which may vary acrossdifferent conduction paths.

The heart sounds-validated beats can also be differentiated from thosenot obtained or validated by way of heart sounds data (such as byforming two classes of beats, with each class processed separately).Alternatively, beats that do not have the benefit of “full” processing(i.e., use of R point in ECG to validate heart sounds data, and thenusing this data to obtain or validate B, C or X points) can beidentified or segregated from those which do have full processing.Myriad other ways of using quality or confidence assessments relative tothe obtained cardiac data will be recognized by those of ordinary skillgiven the present disclosure.

Moreover, When the S1 and S2 sounds are “confidently” identified (forexample, with the confidence metric exceeding a prescribed condition orvalue), they can be used to identify one or more ICG waveformcharacteristics or features that correspond to other events. Forexample, the S1 and S2 sounds can be correlated to the aforementionedICG “B” and “X” points, which are typically associated with the aorticvalve opening and closing, respectively. Hence, by uniquely knowing theICG waveform characteristics that relate to aortic valve opening andclosing, ICG signals can more reliably identify the B and X points, andthereby more accurately determine a variety of hemodynamic parameters.

It will be recognized that the foregoing confidence measure orparameter(s) can also be extended to the B and X point determinations,and even the hemodynamic parameters if desired. Much as one weak linkaffects the overall strength of a chain, a low-confidence S1 and/or S2detection can adversely affect the confidence level of the B and/or Xpoint determinations, and hence any derivative or subsequentdetermination (such as e.g., cardiac output). Conversely, through use ofthe techniques of the present invention, the S and S2 sounds can be morereliably determined (since they are correlated to a known reference),and hence any derivative or subsequent determinations based on these“improved” S1 and S2 sounds will benefit accordingly, and this can berepresented numerically, heuristically, or in another fashion to theclinician.

This also underscores one salient benefit of the techniques describedherein; i.e., an increase in the clinical “robustness” of the system.Specifically, under prior art approaches, low confidence in one or moreparameters (such as B or X point) necessarily provides a “weak link” inthe ICG chain by reducing the confidence in the calculated cardiacoutput (CO). However, by more accurately determining (or simplyvalidating the determination of) the B and X points, the confidence inthe CO measurement is also improved. Stated differently, thedetermination of B and X points can be more tenuous (whether due tonoise, difficult-to-evaluate waveforms of certain patients, etc.), sincethe R-point confirmed heart sounds will aid in reliably pulling thesepoints “out of the noise”. Without the S1 and S2 information, prior artsolutions can tolerate less noise, interference, or waveform anomalysince there is no complementary source of information.

Similarly, heart sounds can often be obscured by internal or externalacoustic or other noise sources, and hence are not always a reliableindicator. Therefore, the present invention contemplates that there maybe times when the heart sounds information is not available (or cannotbe confidently determined, even with the aforementioned ECG R pointreference), at which point the use of this data is suspended for aperiod of time, and/or until its confidence level increases. Again, thesystem is more clinically robust, since its output is not whollydependent on one parameter or the other, they each rather act in concertto enhance the confidence of the resulting measurement, but are alonemay not be individually critical to the measurement.

It will also be appreciated that the foregoing parameters andcharacteristics may be markedly different in different subjects; hence,the techniques of the present invention advantageously afford theability to uniquely “fingerprint” each individual measured.Specifically, by using the R point of a particular individual todetermine (with good confidence) the occurrence of the S1 and/or S2sounds for that same individual, and using these sounds to enhance theconfidence or reliability of the ICG waveform features of interest(e.g., B and X points) for that individual, a unique and high-confidencecorrelation between R point, S1/S2 sounds, and ICG B and X points isestablished for each subject. This data can also be stored for futurereference, not only for use in treating that same subject irrespectiveof location (such as via transmission over the Internet or anothernetwork), but also as part of establishing a database of thesecorrelations. Such a database might comprise, for example, otherpotentially relevant data for the individual (e.g., weight, height, age,body mass index, relevant conditions, medications at time thecorrelation was obtained, pulse rate, blood pressure, etc.), whichenables either a human-based (physician) or algorithmic analysis of thedata across multiple subjects to identify any statistically significantcorrelations therein. For example, it might be determined throughanalysis of this data for many individuals that certain ICG waveformcharacteristics become: more prominent, more reliable, time-shifted withrespect to other events, and so forth as a function of age. Or, certainICG or heart sounds characteristics may only present themselves incertain classes of patients (e.g., those with CHF, obese patients,patients with lung congestion, etc.). The foregoing processes may alsobe implemented in a dynamic fashion, thereby providing even greateradaptability and accuracy of the system. Specifically, the correlations,characteristics or references for a given individual may change as afunction of time, condition, etc. For example, on one day, the reliabledetermination of S1 and S2 may yield a first set of ICG characteristicsthat help accurately determine B and X points. However, on a differentday (same subject), other ICG characteristics may be more useful orreliable. Or, there may be marked changes between when that subject iswaking and ambulatory versus sedated (such as when under anesthesia).Advantageously, the evaluation algorithms of the present invention canbe made adaptive so that the model applied to each subject can bealtered as a function of time or condition, so as to determine theoptimal correlation. For example, in one variant of the algorithms, afirst R point and S1/S2 correlation is made, from which a first B and Xpoint identification is then made. As previously described, a confidencelevel can be ascribed to all or portions of this determination, so as toprovide some basis for future comparison. After a period of time, thealgorithm then repeats this process, identifying the R point and S1/S2sounds again, and then again correlating to ICG characteristics for Band X point determination. However, if the confidence level of thesecond determination is better than the first, the algorithm may selectthe second set of data for subsequent use. In this fashion, the systemis always attempting to improve the confidence level of its results bychoosing a characteristic model or correlation that produces the bestconfidence. This “self healing” approach can be implemented based on anynumber of different logical schemes, such as averaging (e.g., take nsamples and then average results, and compare to a subsequent average ofn different samples), trend (e.g., if n successive subsequentdeterminations provide increased confidence, use one or both of thesubsequent determinations over a prior one), and the like.

Use of heart sounds in combination with ICG waveforms and ECG waveformsalso advantageously facilitates another capability; i.e., theidentification of one or more new ICG fiducial points that may beclinically significant. For example, it may be determined that certainpatients (or classes of patients) exhibit a certain artifact or featurewhich is not a B, C or X point per se, but none-the-less provides auseful reference for CO or other hemodynamic measurements. Suchartifacts may not be a “peak” or “trough”, but perhaps another shape orevent of interest (e.g., inflection point, bump, irregularity, etc.).This detection or determination may be made for example algorithmically(e.g., via a computer program adapted to analyze and recognize certainwave shapes or features), or manually (e.g., by a trained physician), orboth (e.g., via application software which allows a physician or othercaregiver to review and assist in the identification and selectionprocess). See the discussion of waveform assessment and shape analysisprovided subsequently herein.

Yet another benefit of combining ICG, ECG and heart sounds dataaccording to the exemplary embodiment described above is that theinformation from these different monitoring modalities can be used incomplimentary ways to identify patient conditions that may needattention. For example, in one variant, if the monitored heart soundscontain the presence of an “S3” or “S4” heart sound, which may beindicative of a left ventricular failure (S3), or myocardial infarction(i.e., heart attack) or shock (S4), as previously described. Thisinformation may be combined with (or evaluated in light of) the ICGand/or ECG characteristics and interpretations (such as for example STsegment depression or elevation and suspected presence of t-wavealternans, which act as “flags” for the presence of certain conditions),to more definitively diagnose and evaluate a patient's condition. Hence,the presence of an S3 or S4 sound can in one embodiment be used as athreshold or triggering event for more detailed analysis of thecorresponding ICG and/or ECG data, such as via an algorithm.Alternatively, this could cause the physician to have the subjectperform physical movement or a maneuver (such as bending over at thewaist, rolling on their side, standing up, sitting down, exercising,etc.). See e.g., the exemplary logical flow of FIG. 1a , wherein thepresence of S3 or S4 can be used to institute a logical process by whichother data sources (e.g., ICG and/or ECG) can be used to confirm thepresence of a given condition (or demonstrate the presence ofcorrelations within the different sources, which can then be used as aninput to a recognition or diagnostic algorithm).

In another variant, clinical testing performed by the Assignee hereofhas produced ICG waveform data that shows characteristics that arebelieved to be associated with regurgitation of blood from poor heartmuscle performance. Heart sounds can contain acoustic “murmur”information that augments and can be used to confirm this association,and make the detection of this murmur condition more reliable. Aspreviously described, this measurement can also advantageously be usedto optimize pacemaker settings of AV and VV timing for optimal heartmuscle performance; see, e.g., U.S. patent application Ser. No.10/453,820 filed Jun. 2, 2003 entitled “Physiologic Stimulator TuningApparatus and Method”, previously incorporated herein.

In another embodiment of the invention, selective event or datascreening or rejection can be applied to the heart sounds, ICG, and/orECG signals in order to add additional clinical robustness. See, e.g.,co-owned and co-pending U.S. patent application Ser. No. 10/995,920filed Nov. 22, 2004 entitled “Method and Apparatus for Signal AssessmentIncluding Event Rejection”, incorporated herein by reference in itsentirety, which discloses a method of assessing physiologic (e.g.,hemodynamic) parameters within a living subject through analysis ofcontinuous or non-continuous waveforms, including artifacts within thesewaveforms. This assessment includes enhanced or “intelligent” rejectionof certain portions of the waveform(s). By accurately rejecting or notrejecting these portions of the analyzed signals, greater accuracy andclinical robustness are provided. Furthermore, a greater level ofconfidence in the physiologic data obtained (or data derived therefrom)is also provided through use of this approach.

Moreover, various waveform assessment techniques may be used consistentwith the present invention to inter alia more accurately determinefiducial points, and enhance the clinical robustness of the system. See,e.g., U.S. Pat. No. 7,043,293 issued May 9, 2006 and entitled “Methodand Apparatus for Waveform Assessment”, incorporated herein by referencein its entirety, which discloses methods and apparatus for detectingartifacts or features with one or more time-variant information streams(e.g., waveforms). In an exemplary embodiment adapted for use inidentifying (and utilizing) artifacts in the cardiograms of a humansubject, the invention comprises computer code running on a digitalprocessor which is adapted to analyze the subject's ECG waveforms toidentify atrial and ventricular pacing spikes. When these spikes aredetected, they may substitute as Q points during definition of the AZsearch interval for B, C, and X points in a thoracic impedance waveform.Such searches may be conducted using, for example, the wavelet transformmodel described in co-pending and co-owned U.S. Pat. No. 6,561,986entitled “Method and Apparatus for Hemodynamic Assessment includingFiducial Point Detection” previously incorporated herein. Pacing spikedetection in the aforementioned exemplary application incorporates someaspects of artificial intelligence, in that it is desirable to detectspikes of varying amplitude, with variable time delays between the A andV spikes, in the presence of noise also having a variable amplitude.This is accomplished using a golden section search optimizationtechnique, in conjunction with a fuzzy model. The golden section searchidentifies spikes or other artifacts based primarily on their shape asopposed to amplitude or other criteria, thereby significantly increasingthe robustness of the detection algorithm.

In another aspect of the invention, the physiological process ofregurgitation can be identified and/or assessed using the presentinvention. In one embodiment, an ensemble of indicia (including forexample the ECG and ICG waveform, and heart sounds) is used to moreaccurately confirm the presence of regurgitation, or alternativelylocalize where to look for the event. More specifically, in oneembodiment, unique ICG waveform characteristics that have beenclinically identified to be likely indicative of regurgitation can becorrelated with expected heart sound murmurs. This murmur confirmationmay allow physicians to more reliably identify dangerous or undesirableheart conditions. This capability may be especially useful in, interalia, pacemaker applications where adjustment of the AV or VV (or both)settings of the pacemaker is being conducted, such as forresynchronization of the heart. Exemplary pacemaker tuning andassessment methods and apparatus are described in co-owned andco-pending U.S. patent application Ser. No. 10/453,820 entitled“Physiologic Stimulator Tuning Apparatus and Method” filed Jun. 2, 2003,which is incorporated herein by reference in its entirety, although itwill be appreciated that other methods and apparatus may be usedconsistent with the present invention with equal success.

In another aspect of the invention, the length (duration) of one or moreheart sounds is determined and used for inter alia fiducial point orartifact/event identification or location. This duration can be readilydetermined by, for example, measuring amplitude as function of time, andthen measuring the duration from the onset point (i.e., where amplitudeis a prescribed frequency or set of frequencies increases significantlyor above a prescribed threshold value) to the termination point (i.e.,where the amplitude decreases significantly or to below a thresholdvalue). Other schemes for measuring duration may be used as well.

In another variant, the duration of the heart sound(s) relative to QRScomplex duration or length is evaluated. This approach gives informationregarding the electrical activity of the heart relative to its auralactivity. Moreover, the position of one or more ICG fiducial pointswithin the heart sound(s) itself may be determined and evaluated.

Unified Sensor Apparatus

In another salient aspect of the invention, an improved sensor apparatusis disclosed. FIGS. 2a and 2b illustrate one exemplary embodiment of thesensor according to the present invention. In this embodiment, thesensor 200 comprises a disposable sensor generally similar to thoseutilized for ICG measurements, although this is not a requirement. Onesuch exemplary electrode configuration is shown in U.S. Pat. No.D475,138 issued May 27, 2003 entitled “Electrode for Use on a LivingSubject”, incorporated herein by reference in its entirety. See alsoU.S. Pat. No. D471,281 issued Mar. 4, 2003 of the same title, alsoincorporated herein by reference in its entirety. Unlike a conventionalICG electrode, however, the exemplary disposable sensor of FIGS. 2a-2bcombines the ability to detect heart sounds, ICG and ECG, all via thesame sensor 200. As shown, this embodiment of the sensor 200 comprises apatch like substrate 202 with two terminals 204 a, 204 b. The terminalsmay have a predetermined centerline terminal spacing (d in FIG. 2a ) ifdesired, such as according to the teachings of U.S. Pat. No. 6,636,75410/21/2003 entitled “Apparatus and Method for Determining Cardiac Outputin a Living Subject”, incorporated herein by reference in its entirety.The sensor 200 also optionally utilizes an asymmetric terminal size,such that one terminal 204 a is smaller than the other 204 b. Note thatthe different sized terminals provide utility in the use of the sensorsto assure proper device connection.

Additionally, the sensor 200 comprises a chamber 210 for couplingacoustic emissions (e.g., heart sounds) to an external device asdiscussed subsequently herein. In one variant, the chamber 210 comprisesan acoustic condenser or focusing/amplification mechanism of the typewell known in the acoustic arts. The chamber is centrally located, andcoupled to the surface of the tissue of the subject (see FIG. 2b ) so asto channel acoustic energy to a receptor device 212 disposed atop orproximate the chamber 210. In one embodiment, the receptor comprises apiezoelectric device (i.e., one that generates a potential as a resultof applied pressure oscillations such as sound) of the type well knownin the arts. In another embodiment, the sensor comprises apiezoresistive device; i.e., one whose resistance varies as a functionof pressure. Myriad other well known technologies for receiving acousticenergy will be recognized by those of ordinary skill (e.g., a diaphragmwith attached coil, microphone, etc.), such technologies also beinguseful with the invention.

The aforementioned sensor 212 may also be fitted with an electrical ordata interface (described below) of various types so as to permit theacoustic data to be transmitted to an external or host device such as anICG module or the like. See, e.g., the exemplary module and othertechnology described in U.S. Pat. No. 6,602,201 issued Aug. 5, 2003entitled “Apparatus and Method for Determining Cardiac Output in aLiving Subject”, incorporated herein by reference in its entirety, forone exemplary ICG module configuration useful with the presentinvention. In one embodiment, a single lead is utilized to interfacebetween the disposable sensor and the host device. In one exemplaryconfiguration, the connector used for each lead comprises a simplifiedelectrical connector of the type generally described in co-owned andco-pending U.S. Pat. No. 7,214,107 to Powell, et al issued May 8, 2007entitled “Electrical Connector Apparatus and Methods”, incorporatedherein by reference in its entirety, although any number of otherdifferent connector configurations may be used.

One approach for the unified sensor implementation 200 comprises use ofthe same signal line(s) for the ICG, ECG and heart sounds signals,thereby obviating additional signal paths. These signals are separatedvia any number of different well-known techniques such as e.g., viafrequency characteristics, and/or with signal separation algorithms. Forexample, in one embodiment, the ECG signals are in the frequency rangeof 0.05 Hz to 120 Hz, while S1 and S2 heart sounds have similarfrequency characteristics in the range of about 20-150 Hz. However, ICGis usually measured at much higher frequencies around 70 khz, and thisdifference can be used as a basis for separation. This approachadvantageously allows for the use of a single electrical interface(e.g., connector) as previously described. The signals from the acousticsensor element 212 may be detected through the same connections as usedfor the ECG and ICG signals. As another approach, the disposable heartsound, ECG and ICG sensor 200 may be used with one or more additionalleads so the heart sounds and the ECG signals can be separated infrequency.

In another variant of the invention, a cable used to transfer signalsfrom/to the sensor 200 also includes the piezoelectric/piezoresistivedevice or microphone integral therein, thereby further reducing the costof the disposable sensor. For example, the chamber 210 of this variantmay have a receptacle or aperture formed therein, where the cable (withacoustic sensor) can be plugged into. When monitoring is complete, thecable and acoustic sensor 212 are retracted, and can be re-used, whilethe sensor 200 is merely disposed of.

In another embodiment, a substantially unified connector may be usedwith the sensor 200, so as to obviate having to individually place orconnect two or more signal leads as in the prior art. For example, inone variant, a unified connector that allows simultaneous attachment to(i) both of the terminals 204 a, 204 b of the sensor 200; and (ii) aseparate electrical interface for the acoustic sensor 212, is provided.This unified connector may also be polarized (i.e., only fits on oneway, so as to accommodate the differently sized terminals 204 aspreviously described. In another variant, the analog signals of thesensor 212 are routed to one or the other (or both) of the ECG/ICGterminals, and hence the unified connector need only support twoelectrical interfaces (one for each terminal 204).

In another embodiment, the unified connector can include within it theacoustic sensor or microphone 212, so that when the connector is pluggedor mated onto the sensor 200, the acoustic sensor 212 is mated up with areceptacle or acoustic channel, thereby allowing for clear reception ofheart sounds. Likewise, when the unified connector is removed, theacoustic sensor or microphone 212 travels with the connector.

Alternatively, a traditional signal cable arrangement can be used forthe ECG/ICG signals obtained from the terminals 204 of the sensor 200,while a separate wired or wireless interface can be used to transmit theheart sounds signals. For example, in one variant, low cost RFID (radiofrequency ID) technology of the type well known in the art can be usedto transmit data from the sensor 200 to a remote device. As is wellknown, such RFID devices may be active (i.e., internally powered) orpassive, and may also backscatter energy in a modulated fashion. Hence,in one configuration, the sensor 200 is adapted to backscatter modulatean interrogation signal, the modulation comprising data obtained fromthe analog heart sounds sensor 212, which is converted to the digitaldomain via an A/D converter (not shown). In this fashion, the RFIDdevice (which may be very small, and embedded within the sensor patch202 or other component if desired) can generate a binary data streamthat is transmitted off-sensor with no wires and no requirement forindigenous power. However, active RFID devices may also be usedconsistent with the invention if desired.

In yet another embodiment, a capacitive or inductive data interface ofthe type well known in the art is used, so as to permit wirelesstransfer of data from (and to) the sensor 200. For example, one variantof the sensor comprises a capacitive interface, wherein the position ofa first at least partly conductive surface or membrane (disposed on thesensor 200) is varied or modulated by the action of the acoustic heartsounds. A second surface or membrane, associated with the cable orunified connector as previously described for example, is placed inclose proximity to the first surface, with air or another materialacting as a dielectric between the two surfaces. As is well known, thevariation of spacing between the two at least partly conductive surfaceswill cause a variation in the capacitance of the assembly, and thisvariation or modulation of capacitance can be used to generate anelectrical signal to carry information to the host device as previouslydescribed. Similarly, the variation of an inductive coil or other suchapparatus may be used to transfer information.

In yet another embodiment, a technology that replaces air pressurechanges with electric field changes may be used. See, e.g., theexemplary “electromagnetic diaphragm” developed and sold by ThinklabsMedical, LLC of Centennial, Colorado for one commercially availabledevice that may be adapted for use herewith. In effect, diaphragmmovement represented as an electrical signal can be amplified andprocessed. The resulting electrical signal has a high conformance withthe air pressure changes at the diaphragm of a traditional stethoscope,ensuring that the electrical signal captures the authenticity ofstethoscope sound. In one variant, the electromagnetic diaphragm (EmD)is coated internally with a conductive surface. Behind the diaphragm issituated a conductor (e.g., metal plate) which is charged with avoltage, thereby establishing an electric field behind the diaphragm.

As the diaphragm moves, the voltage induced on the plate changes due tovariation of the electric field intensity as a function of position.Such implementations advantageously produce a sound familiar to theclinician, yet amplified and processed to extract the optimalcharacteristics.

In another embodiment (FIG. 2c ), a thin-film piezoelectric orpiezoresistive element 270 of the type well known in the art may be usedto generate electrical signals relating to applied sound waves (e.g.,heart sounds). As is known, such devices alter their electrical outputor resistance, respectively, as a function of applied pressure(variations). Such devices may be made quite small and thin, and evenfor example disposed on or formed as a film or layer. Such film or layercan be used with the ICG/ECG patch 272 described elsewhere herein in oneembodiment (and even utilize the existing electrical terminals 274 a,274 b and leads if desired, such as via conductors 276 which are routedfrom the piezoresistive or piezoelectric element 270), thereby making asmall form factor integrated device. Alternatively, the film or layercan be used as part of a separate device which may be applied at aclose-by or different location as needed.

Also, in another variant, the sensor is equipped with a low cost buffermemory (not shown) that allows acoustic data that has been digitized tobe stored and subsequently read out (e.g., “bursted”) when acommunication channel is established, such as when a reader wand orprobe is passed over the sensor 200, or when the sensor comes insufficient proximity of a reader device. The sensor could also workwith, and require the connector to form a detector.

It will be recognized that while exemplary embodiments of apparatus andmethodology are described herein in terms of the cardiac outputdetermination, the invention also be readily used in assessing otherhemodynamic parameters, such as without limitation the pre-ejectionperiod (PEP, the interval between Q point and B point), isovolumetricrelaxation time, presence of excess intravascular fluid, presence ofexcess pulmonary fluid and the like, and accordingly is not limited tothe measurement of stroke volume, cardiac output, or QRS complexidentification.

Apparatus for Hemodynamic Assessment—

Referring now to FIG. 3, an apparatus for measuring hemodynamicproperties associated with the cardiovascular system of a living subjectis described. In the illustrated embodiment, the apparatus is adaptedfor the measurement of the cardiac output of a human being, although itwill be recognized that other hemodynamic parameters and types of livingorganism may be evaluated in conjunction with the invention in itsbroadest sense.

The exemplary embodiment of the apparatus 300 of FIG. 3 fundamentallycomprises a plurality of electrically conductive sensors or electrodes200 (with individual terminals 204 a, 204 b) of the type describedherein with respect to FIGS. 2a-2b for supplying a current and measuringvoltage (and impedance) from the subject non-invasively; a currentsource 304 coupled to at least a portion of the electrodes 200 forproviding the alternating (AC) electrical current supplied to thesubject; discrete analog circuitry 306 for preconditioning the analogimpedance and ECG waveforms derived from the electrodes 302, ananalog-to-digital converter (ADC) 307 for converting the conditionedanalog signals to a binary digital format; a digital processor 308operatively connected to the ADC 307 for analyzing the digitalrepresentations of the conditioned ECG and impedance waveforms; a buffermemory 310 for storing conditioned data prior to fiducial pointdetection; program and data memories 311, 313, for storing programinstructions and data, respectively; a mass storage device 315, an inputdevice 317 for receiving operation command and data from the apparatususer, and a display device 318 for displaying information such as dataand waveforms, as well as applications program interface, to the user.One or more algorithms (e.g., computer programs or code) used for, interalia, the aforementioned analysis of the ECG, impedance, and/or heartsounds waveforms are disposed on the apparatus as well, such as beingstored on a mass storage device (e.g., HDD), loaded into program memoryof the digital processor 308, etc. Many functions may be implemented infirmware or even hardware if desired, as will be appreciated by those ofordinary skill in the computer arts. See also the discussion ofexemplary computer programs provided subsequently herein.

The electrodes 200 of the embodiment of FIG. 3 comprise so-called “spot”electrodes of the type well known in the medical arts, although it willbe recognized that other types of electrodes, including band electrodesmay be substituted. As used herein, the term “spot” electrode includesboth single- and multi-terminal electrodes adapted for use in alocalized area of the subject's physiology, such as e.g., those of FIGS.2a -2 b.

In operation, the apparatus 300 generates an effectively constantcurrent (via the current source 304) or constant voltage which isapplied to certain ones of the terminal(s) 204 of the electrodes 200.The applied current derived from the current source 304 is a 70 kHz sinewave of approximately 2.5 mA maximum RMS. The measured voltageassociated with the aforementioned sine wave is on the order of 75 mVmaximum RMS. These values are chosen to advantageously minimize electricshock hazard and provide adequate signal to noise characteristics,although it will be appreciated that other frequencies, currents, orvoltages may be substituted. The construction and operation of ACcurrent sources is well known in the electronic arts, and accordingly isnot described further herein.

The preprocessor 306 and associated signal processing apparatus is inelectrical communication with other electrodes 200, from whichpotentials (voltages) are measured. In the selected frequency range ofthe AC signal (e.g., 70 kHz), the typical impedance associated with ahuman subject's skin is 2 to 10 times the value of the underlyingthoracic impedance Zr(t). To aid in eliminating the contribution fromskin and tissue impedance, the apparatus of the present invention usesat least two, and typically four electrode arrays 200 a-200 d formeasurement, as shown in FIG. 3. In a simple application, one electrodearray 200 a comprising a stimulation electrode terminal 204 a and ameasurement electrode terminal 204 b is applied above the thorax of thesubject, while a second electrode array 200 b (similarly having astimulation electrode terminal and measurement electrode terminal) isapplied below the thorax. The AC current (or pulsed waveform, or DCcurrent, or another waveform shape such as sawtooth, square, NRZ, etc.)from the current source is supplied to the stimulation electrodeterminals. Current flows from each stimulation electrode terminal 204 athrough each constant skin impedance, Z_(sk1) or Z_(sk4), each constantbody tissue impedance, Z_(b1) or Z_(b1), and each constant skinimpedance, Z_(s2) or Z_(sk3), to each measurement electrode terminal 204b. The voltages at the measurement electrode terminals 204 b aremeasured and input to a differential amplifier circuit 327 within thepreprocessor 306 to obtain the differential voltage, V_(T)(t). Thedesired thoracic impedance, Z_(T)(t), is then obtained using therelationship of Eqn. 1.

$\begin{matrix}{{Z_{T}(t)} = \frac{V_{T}(t)}{I_{T}(t)}} & \left( {{Eqn}.\mspace{14mu} 1} \right)\end{matrix}$

As shown in FIG. 3, two sets of electrode arrays 200 a-d mayadvantageously be used to monitor the impedance associated with the leftand right portion of the thorax in the present invention. When eightelectrode terminals (four arrays 200 a-d each with two terminals 204 a,204 b) are used in this manner, the four measurement arrays are alsoused to obtain an electrocardiogram (ECG). As previously discussed, theQ wave of the ECG QRS interval is used to, inter alia, determine thesubject's heart rate, identify the QRS complex and Q and R points, andas an input to the fiducial point detection algorithm for the impedancewaveform. Heart sounds information obtained from the sensors 200 (viaacoustic sensors 212) is also passed via the electrical or wirelessinterface previously described to the apparatus 300 for processing asset forth above. In one embodiment, the heart sounds information iscarried as electrical signals via the same conductors used for ICG/ECGsignals. In another embodiment, the heart sounds information is carriedvia a separate set of electrical conductors. In yet another embodiment,the auditory signals generated by a transducer disposed on the subjectbeing monitored are converted into electrical signals, which are thenconverted to electromagnetic radiation (e.g., radio frequency or IR) andsent over a wireless data link. In yet another embodiment, the auditorysignals (pressure variations) are transmitted via an interposed medium(such as via an audio tube) to another component and then converted toelectrical signals.

It will also be appreciated that the exemplary embodiments of theinvention utilize data acquisition apparatus that provide simultaneousor near simultaneous data (or at least a chronological or otherreference so that the various types of data can be properly synchronizedwith one another later on). Signals may optionally be, for example,indexed or referenced to a clock signal generated within the apparatus(such as by a crystal clock generator or the digital processor) anddistributed to various components. Signal acquisition, transit andprocessing times may also need to be considered and accounted for (suchas via, e.g., insertion of a positive or negative time index offset, soas to chronologically align the various data). Such techniques are wellknown to those of ordinary skill in the electronic and signal processingarts, and accordingly not described further herein.

It is noted that the apparatus 300 described herein may be constructedin a variety of different physical configurations, using a variety ofdifferent components, and measuring a variety of different hemodynamicparameters. For example, some or even all of the foregoing componentsmay be physically integrated (such as in an application specificintegrated circuit incorporating a DSP core, memory, “front” end analogprocessing, and ADC in a single piece of silicon), and/or thefunctionality associated with multiple components performed by a singlemulti-function component (e.g., a processor adapted to performcalculations associated with the wavelet transform methods disclosedherein, as well as host functions such as video display, busarbitration, etc.). One exemplary configuration comprises a PC-baseddevice of the type well known in the art, having a host microprocessoras well as the aforementioned preprocessing and signal processingfunctionality in the form of a separate DSP in data communicationtherewith. In yet another embodiment, the apparatus comprises a mobilepersonal computing device (such as a personal digital assistant, orPDA), which is adapted to receive input data from the electrodes 200 andanalyze the data to produce a corrected measurement of cardiac output.It will also be recognized that other portable devices, such as laptopcomputers, calculators, and personal organizers, may conceivably beconfigured to run the computer program(s) of the present invention. Suchportable devices are readily adapted to the methods of the presentinvention, since as a result of the invention's advantageous use ofcomparatively simple wavelet transforms, the processing and storagecapability needed to implement the algorithm is decreased. Furthermore,a variety of different methods of transmitting the input sensor (i.e.,electrode) data to these devices may be used, including networkedcomputers, or even wireless data links as previously described.

Furthermore, cardiac output, LVET, SV, or other measurements generatedby the foregoing apparatus 300 may also optionally be stored in thestorage device 315 for later retrieval, or output to an external devicesuch as a printer, data storage unit, other peripheral component via aserial or parallel port if desired. Furthermore, the apparatus 300 maybe networked to another computing device or database (not shown) wherebythe data generated by the apparatus may be remotely analyzed or stored.Transmission of output data to such remote devices may be accomplishedusing a variety of well understood methods, such as by local areanetwork (LAN), intranet, Internet, fiber-optic systems, or radiofrequency (wireless) devices.

It will be further recognized that while the apparatus 300 of theinvention is described herein as a substantially discrete or“stand-alone” system, the invention may be adapted to act as a plug incard, module, or other complementary device (including any supportingsoftware) for an existing ECG or patient monitoring system that utilizeselectrodes. Hence, the invention can advantageously be “retro-fitted” tosuch prior art systems, thereby extending the utility of thepre-existing system, and potentially obviating the purchase of entirelynew equipment.

Computer Program—

A computer program for implementing the aforementioned methods of heartsounds, impedance and ECG waveform analysis is now described. In oneexemplary embodiment, the computer program comprises an object(“machine”) code representation of an assembly source code listingimplementing the analysis methodologies previously described herein,either individually or in combination thereof. While assembly languageis used for the present embodiment, it will be appreciated that otherprogramming languages may be used, including for example VisualBasic™,Fortran, C, and C⁺. The object code representation of the source codelisting is compiled and disposed on a media storage device of the typewell known in the computer arts. Such media storage devices can include,without limitation, optical discs, CD ROMs, magnetic floppy disks or“hard” drives, tape drives, or even magnetic bubble memory. The computerprogram further comprises a graphical user interface (GUI) of the typewell known in the programming arts, which is operatively coupled to thedisplay and input device of the host computer or apparatus 300 on whichthe program is run.

In terms of general structure, the program is in one embodimentcomprised of a series of subroutines or algorithms for implementing themethodologies described herein based on measured parametric data (e.g.,the “input parameters” previously defined) which are provided to thehost computer. In a second embodiment, the computer program comprises anassembly language/micro-coded instruction set disposed within theembedded storage device, i.e. program memory, of a digital signalprocessor (DSP) or microprocessor associated with the foregoinghemodynamic measurement apparatus of FIG. 3.

Method of Providing Treatment—

Referring now to FIG. 4, a method of providing treatment to a subjectusing the aforementioned methods is described. While the followingdiscussion is cast in terms of the aforementioned methods and algorithmsadapted for determining cardiac output, it will be recognized that themethod or providing treatment described herein is more broadlyapplicable to treatment based on the assessment of any hemodynamicproperty or parameter based on e.g., multi-source analysis.

As shown in FIG. 4, the method of providing treatment 400 generallycomprises first disposing a plurality of impedance cardiographyelectrodes (see e.g., FIGS. 2a and 2b ) with respect to the thoraciccavity of the subject per step 402. As previously discussed, theelectrodes 200 are the single or multi-terminal type with heart soundscapability (or other suitable configuration), and are disposed above andbelow the thorax of the subject such that at least one stimulationterminal and one excitation terminal are above and below the thorax.

Next, the impedance waveform (and ECG and heart sounds) data of thesubject are measured non-invasively via the electrodes per step 404;specifically by applying a constant AC waveform to the stimulationterminal(s), and measuring the resultant voltage at the measurementterminal(s), as well as utilizing the acoustic sensor 212 previouslydescribed for heart sounds. In step 406, the stroke volume of thesubject's cardiac muscle during at least one cardiac cycle is determinedusing the multi-source detection and validation methodologies previouslydiscussed herein. The stroke volume is determined from the derivedhemodynamic characteristics of the waveform; such as for example in oneembodiment via LVET and dZ/dt_(max). The cardiac output (CO) of thesubject is next determined in step 408 based on the stroke volumedetermined in step 406, and the heart rate (HR) derived from the subjectfrom, for example, the ECG waveform or the heart sounds sensor.

Per step 408, a diagnosis or assessment of the subject's condition mayalso be performed, such as based on the identification of one or moreartifacts or shapes of interest (e.g., the presence of S3 or S4, andcorrelation/confirmation thereof, as shown in FIG. 1a ), as previouslydescribed.

Lastly, a course of treatment is determined and provided to the subjectbased on the cardiac output (CO) of step 410. Such course of treatmentmay include, for example, the intravenous injection of pharmacologicalagents, angioplasty, or other such measures aimed at increasing cardiacoutput or otherwise stemming further degradation of the subject'scardiac function.

It will be noted that the methods of treatment described herein may beused in a “feedback” fashion; i.e., the response to one or more coursesof treatment or therapy can be monitored for indications of proper (orimproper) patient response, or unexpected reactions. In this fashion,the course of treatment or therapy can be confirmed. Moreover, theactual monitoring of the subject can be altered based on this feedback;for instance, if a patient being monitored is going into shock, or beinganesthetized, the pulse or cardiac performance may be affected, therebynecessitating different monitoring parameters/settings, or evendifferent strategies.

Defibrillation Apparatus and Methods—

In another aspect of the invention, an improved defibrillation apparatusand methods are disclosed. Specifically, the use of a heart soundssensor provides data regarding the shock/no-shock decision. See, e.g.,U.S. Pat. No. 7,149,576 issued Dec. 12, 2006 entitled “Apparatus andMethod for Defibrillation of a Living Subject”, incorporated herein byreference in its entirety, which discloses defibrillation apparatus andmethods which use impedance cardiography techniques for accuratelydetermining if and when a countershock should be applied to the subject.This approach for determination of shockable and nonshockable rhythms,including for example VT (Ventricular Tachycardia) and SVT(Supra-ventricular tachycardia), determines if significant and pulsatilecardiac output (blood flow through the heart) is present with eachheartbeat. In one exemplary embodiment of the apparatus, electrodes(which may also have a predetermined terminal spacing) are utilized toensure ICG waveform features are captured with sufficiently highresolution. Pacing spike detection is implemented to preventmisclassification of pacing spikes as R points. A wavelet algorithm forefficient R point detection during arrhythmias is also used inconjunction with the foregoing. Various wavelets and scaling functionsare utilized as part of the invention to emphasize certain features ofinterest associated with the input impedance and/or ECG waveformsobtained from electrodes positioned on the subject's thorax. Theresulting emphasized feature in each wavelet transform is then detectedto obtain a fiducial point (e.g., B, C, X for the impedance waveform,and R for the ECG waveform). By virtue of its transformation to thetime-scale domain, this wavelet method is more resistant to noiseartifact than empirical waveform processing in the time domain.

Furthermore, no absolute thresholds are used for R, B, C, or X pointdetection in the exemplary embodiment, which increases the ability ofthis algorithm to generalize among waveforms from the cardiac patientpopulation. This capability can also be enhanced through the use ofheart sounds information as previously described herein. The use of adecision model not constrained to discrete values or absolute thresholds(e.g. a fuzzy logic model) ensures that the decision module is capableof such generalization. With efficient beat detection, the variabilityof B point and X point samples can also advantageously be determinedwith higher certainty.

It will be recognized that while certain aspects of the invention havebeen described in terms of a specific sequence of steps of a method,these descriptions are only illustrative of the broader methods of theinvention, and may be modified as required by the particularapplication. Certain steps may be rendered unnecessary or optional undercertain circumstances. Additionally, certain steps or functionality maybe added to the disclosed embodiments, or the order of performance oftwo or more steps permuted. All such variations are considered to beencompassed within the invention disclosed and claimed herein.

While the above detailed description has shown, described, and pointedout novel features of the invention as applied to various embodiments,it will be understood that various omissions, substitutions, and changesin the form and details of the device or process illustrated may be madeby those skilled in the art without departing from the spirit of theinvention. The foregoing description is of the best mode presentlycontemplated of carrying out the invention. This description is in noway meant to be limiting, but rather should be taken as illustrative ofthe general principles of the invention. The scope of the inventionshould be determined with reference to the claims.

We claim:
 1. A sensor apparatus for use in assessing cardiac function ofa living subject, comprising: a substantially unitary base element; aplurality of terminals, wherein the plurality of terminals are utilizedin the communication of electrocardiographic and impedance cardiographicinformation of the living subject to a processing device; an acousticreceptor device; and a chamber configured to couple acoustic emissionsfrom the living subject to the acoustic receptor device.
 2. The sensorapparatus of claim 1, wherein the substantially unitary base element andthe plurality of terminals are of low cost thereby rendering the sensorapparatus disposable.
 3. The sensor apparatus of claim 1, wherein theacoustic receptor device comprises a piezoelectric device.
 4. The sensorapparatus of claim 1, wherein the acoustic receptor device comprises apiezoresistive device.
 5. The sensor apparatus of claim 1, furthercomprising one or more signal lines, wherein the one or more signallines electrically couple the plurality of terminals and the acousticreceptor device to the processing device, and wherein the one or moresignal lines are configured to simultaneously transmitelectrocardiographic, impedance cardiographic, and acoustic informationto the processing device.
 6. The sensor apparatus of claim 1, whereinthe acoustic receptor device is removable and is configured to bereceived in a reception apparatus within the substantially unitary baseelement.
 7. The sensor apparatus of claim 1, wherein the acousticreceptor device is configured for wireless transmission of acousticinformation.
 8. The sensor apparatus of claim 1, wherein the acousticreceptor device comprises an electromagnetic diaphragm.
 9. The sensorapparatus of claim 8, wherein the electromagnetic diaphragm furthercomprises: a substantially conductive coating disposed on a surface toform a coated surface; and a voltage-charged conductor located behindthe coated surface.
 10. The sensor apparatus of claim 1, wherein theplurality of terminals includes a first terminal and a second terminal,wherein the first terminal is a different size than the second terminal.11. The sensor apparatus of claim 1, further comprising wireless meansfor transmitting data from the plurality of terminals and the acousticsensor to the processing device.
 12. The sensor apparatus of claim 11,wherein the wireless means includes an RFID device.
 13. A disposablesensor apparatus for use in determining the cardiac function of a livingsubject, comprising: a patch-like substrate; a first terminal and asecond terminal, wherein the first terminal and second terminal arespaced a predetermined distance relative to each other; an acousticreceptor device, wherein the acoustic receptor device, the firstterminal, and the second terminal are disposed on the patch-likesubstrate; and a chamber configured to couple acoustic emissions fromthe living subject to the acoustic receptor.
 14. The disposable sensorapparatus of claim 13 wherein the acoustic receptor device comprises apiezoelectric device.
 15. The disposable sensor apparatus of claim 13wherein the acoustic receptor device comprises a piezoresistive device.16. The disposable sensor apparatus of claim 13 wherein the acousticreceptor device is removable from the patch-like substrate.
 17. Thedisposable sensor apparatus of claim 13 wherein the acoustic receptordevice is configured to be received in a reception apparatus within thepatch-like substrate.
 18. The disposable sensor apparatus of claim 17wherein the reception apparatus is configured to couple the acousticreceptor device to the chamber.